BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10047292
• 负责人: Philip N. Rather
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10047292
• 关键词: Acinetobacter baumannii; Address; Afghanistan; Agar; Antibiotic Resistance; Antibiotics; Area; Attenuated; Award; Bacteria; Basic Science; Biochemical; Blood Circulation; Cell division; Cells; Collaborations; Defect; Development; Engineering; Fostering; Freedom; Frequencies; Funding; Gene Silencing; Genes; Genetic; Genetic Transcription; Goals; Gram-Negative Bacteria; Health; Hospitals; Human; Infection; Intervention; Iraq; Legal patent; Link; Mentors; Microbiology; Military Personnel; Mus; Nature; Phenotype; Population; Regulation; Research; Research Personnel; Research Project Grants; Resistance; Role; Scientist; Skin Tissue; Soft Tissue Infections; Soldier; Structure of parenchyma of lung; Training; Translational Research; United States Department of Veterans Affairs; United States National Institutes of Health; Universities; Urinary tract; Vaccinated; Vaccines; Virulence; Virulent; War; Work; World Health Organization; beta-Lactam Resistance; beta-Lactamase; beta-Lactams; career; injured; next generation; novel; novel strategies; novel therapeutics; operation; pathogen; post-doctoral training; programs; resistant strain; soft tissue; student training; transcriptomics

Project Summary. The Gram-negative bacterium Acinetobacter baumannii is a leading cause of infections in both the hospital setting and in military personnel injured during wartime. The goal of this Research Career Scientist Award is to continue addressing the mechanisms that regulate virulence and β−lactam resistance in A. baumannii. A high-frequency switch that regulates the transition between virulent (opaque) and avirulent (translucent) forms of A. baumannii will be studied using a combination of genetic and biochemical approaches. The role of a putative bistable transcriptional regulator in the opaque to translucent virulence switch will be investigated by genetic and transcriptomic approaches. A second area of research is focused on the regulation of intrinsic β-lactam resistance in A. baumannii. Our work has identified a novel gene in A. baumannii that is required for intrinsic β−lactam resistance. Inactivation of this gene sensitizes A. baumannii to β−lactams and also confers a prominent cell division defect. This provides the first link between defects in cell division and decreased intrinsic β-lactam resistance and suggests novel interventions that target cell division may sensitize cells to β-lactams. These research projects are highly collaborative and involve VA investigators at both the Atlanta VAMC and the Louis Stokes VAMC in Cleveland, OH. This project will continue to foster these collaborations and allow for the development of new projects. This project will also have an important training component, where mentoring for junior VA investigators will be provided. Lastly, student and postdoctoral training will continue to be an integral component of this research plan, with the goal of developing the next generation of VA scientists by mentoring a CDA-2 awarded project.

项目摘要。 革兰氏阴性细菌鲍曼尼菌是 医院环境和军事人员受伤的感染 战时。该研究职业科学家奖的目标是继续 解决调节A的病毒和β-内酰胺抗性的机制。 鲍曼尼。调节有毒之间过渡的高频开关 （不透明）和鲍曼尼（A. baumannii 遗传和生化方法的结合。推定的角色 不透明至半透明病毒开关中的可振动转录调节器将 可以通过遗传和转录组方法进行研究。第二个区域 研究的重点是调节A。 鲍曼尼。我们的工作已经确定了A. baumannii中的一种新基因 用于固有的β-内酰胺抗性。该基因的灭活感会吸引A. Baumannii 到β-内酰胺，也赋予明显的细胞分裂缺陷。这提供了 细胞分裂缺陷与改善固有β-内酰胺的第一个联系 抗性并提出新的干预措施，靶向细胞分裂可能会感觉到 细胞到β-内酰胺。 这些研究项目高度协作，涉及VA 亚特兰大VAMC和路易斯·斯托克斯VAMC的调查员 克利夫兰，哦。该项目将继续促进这些合作，并允许 用于开发新项目。该项目还将有一个重要的 培训组件，将为初级VA调查人员提供心理。 最后，学生和博士后培训将继续是不可或缺的 该研究计划的组成部分，目的是发展下一代 VA科学家通过为CDA-2授予的项目介绍。